Everything Everywhere All at the Liau Lab

新年快樂！

Happy belated (Lunar) New Year from the Liau Lab! It’s been a really busy past year for us, filled with both science and, well…not-science.

We are all Michelle Yeoh <3

From apple picking to ice skating, we’ve had lots of fun over the past year:

Apple picking, or as the kids like to say, Pick Apple-ing.

Breakfast for dinner at our favorite local IHOP.

Ice skating at the Fenway rink. Brian is a very “down-to-earth” PI.

Enjoying some soondubu at Kaju!

Olivia educates the group on grass jelly desserts at MeetFresh.

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Fun aside, we’ve also been hard at work. In fact, 2022-2023 has really been the year of the Liau Lab—well, at least publishing-wise ;) In case you missed our recent scientific work, here’s a quick summary of our papers from the past year. Note: this is continuing off of our previous blog post—go check that out for our recent publications on molecular glue degraders and more!

Lamina-Inducible Methylation and Hi-C (LIMe-Hi-C)

Chemical biology meets 3D genomics! We developed a new approach to simultaneously look at chromosome conformation, DNA methylation, and lamina positioning. Through this, we found and subsequently characterized intriguing Polycomb-marked subcompartments!

DNMT3A base editor scanning

The lab’s first base editor screen, using an innovative reporter approach to study a nonessential gene! We leveraged an endogenous methylation activity reporter to map sequence-activity relationships across DNMT3A. Following up our screen results, we found a noncanonical DNA binding role for the PWWP histone reader domain. What’s more is that our screening strategy can be applied toward other chromatin regulators!

CRISPR-suppressor scanning

Our lab’s official protocol for CRISPR-suppressor scanning is out in Current Protocols! If you’re interested in mapping drug-protein interactions and identifying resistance mutations, you’ll be interested in checking this out.

DNMT1 activity-based CRISPR scanning

CRISPR screens for allostery? Taking advantage of decitabine, an activity-based DNA methyltransferase inhibitor that is nearly identical to the cytosine substrate, we applied CRISPR-suppressor scanning to look for mutations impacting allostery. We found some interesting ones causing DNMT1 hyperactivation. This paper also has some updated and improved analytical tools for analyzing tiling CRISPR screening data.

This paper is currently accepted in principle and we don’t have the pdf yet, but please enjoy our graphical abstract :3

PRC2 drug-addiction scanning

CRISPR screening a whole complex! We used CRISPR-suppressor scanning to systematically mutate the three core members of the PRC2 complex, discovering mutations that confer drug addiction. These pointed toward a model where lymphoma cells need to be in a “Goldilocks” state—too much or too little H3K27me3 is bad.

We had some fun creating art related to some of these studies, though unfortunately they weren’t selected by the journals for the cover/feature. Well, even if journals don’t appreciate our art, hopefully our blog readers will!

Nick, Allison, and Shelby collaborated to make this artistic representation of our LIMe-HiC method. The lime cross-section represents the nucleus, and the red represents GpC methylation.

Nick made this design representing DNMT3A base editor scanning. The pins represent loss-of-function mutations scattered across DNMT3A, and the compass is an homage to base editing.

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This past year also saw some new faces arriving in our group. We welcomed the skilled organic chemist, Dr. Stefan Harry, as a joint postdoc with the Bar-Peled lab at MGH. Additionally, we said hi to Tobias Hansen, a visiting graduate student from the University of Copenhagen!

Dr. Stefan Harry

Tobias Hansen

We also welcomed three (count ‘em, yep, we’re popular) new CCB graduate students to the lab:

Calvin Hu

Marc Anthony Zepeda

Idris Barakat

In more bittersweet news, we said goodbye to our longtime lab administrator Rebecca. We’re sad to see her go, but luckily she still works in the department so we can say hi :) On the bright side, we welcomed Lizzy Swenson as our new lab administrator, and have had a great time getting to know her!

Rebecca Stillo

Lizzy Swenson

Continuing with bittersweet departures, our lab has experienced some turnover in our researchers as well. Earlier in the year, we had three talented scientists move on to their next positions:

Pallavi, our first biologist postdoc and a stellar scientist, is now a Senior Scientist at Merck. Pallavi launched the protein biochemistry side of the lab and has provided invaluable expertise to numerous projects. More recently, she led our lab’s study applying CRISPR-suppressor scanning to investigate molecular glues.

Jiaming, a superb synthetic organic chemist postdoc, recently returned to California as a Senior Scientist at Ideaya Biosciences. He served as a mentor and wellspring of expertise for many during his time here, and synthesized a huge number of vital compounds, leaving a lasting mark on our lab (and our freezers).

Sam, a talented research assistant, is now attending medical school at the Cleveland Clinic, Case Western Reserve University! Sam was instrumental in biochemically characterizing DNMT1 mutants and also contributed to numerous other projects.

Check out these videos from Jiaming and Sam’s farewell party, by the way:

You may have seen our last blog post, but we also had four talented graduate students defend (Ally, Kevin, Allison, and Amanda). (*suppresses sobbing*)

Kevin Ngan, Ph.D. Kevin is now working at Tessera Therapeutics.

Allison Siegenfeld, Ph.D. Allison is now doing a postdoc in Prof. Karen Adelman’s lab at HMS.

Amanda Waterbury, Ph.D. Amanda is continuing in our lab as a postdoc for the near future.

Ally Freedy, Ph.D. Ally is now finishing the M.D. part of her M.D.-Ph.D. training at HMS.

With so much going on, 2023 has arrived sooner than any of us expected. But you know what? We have even more cooking, science-wise. Stay on the lookout for the YEAR OF THE LIAU LAB, PART 2!

2022 Liau Lab Ph.D.s!

It’s been a wild year with lots of ups and downs, including many beloved labmates leaving. Notably, we had four new Liau Lab Ph.D.s this year! All four of these talented students were among the first students in the lab, and so we wanted to make a special post commemorating their graduations. Stay tuned for another end-of-year blog post documenting our other festivities as well as scientific accomplishments :)

Congrats to Ally, Kevin, Allison, and Amanda!

First up is Ally Freedy, our resident M.D.-Ph.D. who defended in May. Ally was a key player in our lab’s projects studying LSD1 and PRC2 (look out for the latter story coming to a journal near you soon…). In particular, she helped pioneer CRISPR-suppressor scanning, and later in her Ph.D. focused on PRC2 biochemistry, helping to establish protocols for insect cell recombinant protein expression in our lab. Outside of lab, she was extensively involved in Harvard Women in Chemistry, serving as President. She delivered a spectacular defense and is now finishing her M.D. at Harvard Medical School.

Congratulations to Dr. Freedy!

Ally recently received the 2022 Broad Award in Scientific Excellence!

Next up is Kevin Ngan, who defended in October. Kevin has been instrumental in our lab since day 1, serving as an expert in cell culture, NGS, and computational analysis. Many of our lab’s protocols (including pivotal screening- and sequencing-related ones) were in fact written by him (look out for our CRISPR-suppressor scanning protocols paper soon…). Kevin’s contributions have ranged far and wide within our lab, but he has especially been focused on applying CRISPR screening to study molecular glue mechanism of action (see his and Pallavi’s ACS Central Science paper) and mechanisms of allostery in the DNA maintenance methyltransferase DNMT1 (preprint is available on bioRxiv, paper coming out soon!). Beyond his scientific accomplishments, Kevin has been a huge source of support and mentorship to many in the lab and has had an unmeasurable impact on our lab’s culture. He is also an avid rock climbing enthusiast who has gotten most of the lab into the sport. Having finished his Ph.D., Kevin is now working as a scientist at a biotechnology company, Tessera Therapeutics.

Congratulations to Dr. Ngan!

November brought us Allison Siegenfeld’s defense. Allison is our resident computational biology expert and DNA gel enthusiast. From chemical synthesis to large-scale genomics to even fluorescence microscopy, Allison has done it all. She initiated our lab’s research in 3D genomics and, together with Shelby, developed a pioneering approach to look at how DNA is positioned in 3D space within the nucleus, how it contacts other DNA, and the patterns by which it is marked by DNA methylation, all in one simultaneous experiment (check out their Nature Communications paper). She has also served as a computational expert in our lab’s efforts to study LSD1 and PRC2, proving her bioinformatic chops. More than this, she is an enthusiastic mentor, selfless source of advice and support, and a beacon of positive energy. Beyond our lab, Allison has also been highly engaged in the broader CCB community, in particular through her work with the Harvard Women in Chemistry, where she started a mentorship program. In the new year, she will be starting as a Postdoc in Prof. Karen Adelman’s lab at Harvard Medical School, so keep an eye out for her future scientific work!

Congratulations to Dr. Siegenfeld!

Finally, in December we witnessed a truly inspiring defense courtesy of Amanda Waterbury. In Brian’s words, Amanda is “a chemical biologist in the truest sense of the word.” Her graduate work has been exceptionally interdisciplinary, encompassing chemical synthesis, protein biochemistry, mass spectrometry, cell biology, fluorescence microscopy, genetic screening, and more, and she has quickly developed mastery in all of these areas. In particular, she has focused on studying the mechanisms of action of LSD1 inhibitors, ranging from an active site-targeting inhibitor that blocks TF interaction to a puzzling compound that chemically modifies the LSD1 active site. Keep an eye out for her upcoming work in these areas, which should be published in the near future. Beyond this scientific work, Amanda has been a mentor to many and the lab’s authority on all things protein-related (and cat-related). She has selflessly worked to keep the lab running and is the exemplary lab citizen. Her true scientific passion is in chromatin biochemistry, and she will be continuing this work as a Postdoc in Prof. Phil Cole’s lab at Harvard Medical School! Though luckily for us, we still have a bit more time to enjoy her company and expertise before she leaves.

Congratulations to Dr. Waterbury!

These departures are especially bittersweet, as Kevin, Allison, and Amanda are the last of our lab’s first cohort of graduate students. These three helped found the lab and shape everything that we do, and for that we are so thankful. As Brian said, “you never forget your first students.” So, we end this blog post with some photos of Brian with his first mentees.

Congratulations to all!

Publications, Preprints, and PQEs—Oh My!

It’s a bird!… It’s a plane!… no… It’s the latest—

LIAU LAB BLOG POST !!!

Did you miss us? It’s been a hectic year for us, but we are so excited to share the work we’ve been up to. We’ve had a lot of things in the works and 2022 is shaping out to be the year that we unleash the flood on the scientific community. Ready or not, here we come!

Keen followers of our website might have noticed some changes recently. We’ve revamped our website, for starters, and what’s more, we’ve dropped some new publications. Let’s take a quick stroll through them…

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But first of all we have an important announcement to make. The big man himself has finally joined the twittersphere! Help us get him to 1,000 followers (or at least to another fun number before that)!

Please like + subscribe! <3

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Now back to what you’re here for. Without further ado, here are our lab’s peer-reviewed publications from the past year! Click on the pictures to go to the journal site.

The exciting sequel to 2019’s Park et al. paper! We synthesized improved cycloheximide derivatives and collaborated with the Shao lab to perform cryo-EM characterization. A multidisciplinary study spearheaded by Yumi and Eileen.

Drug resistance sounds scary but it’s actually been a driving force for biological discovery. Ally wrote an insightful review on the history of drug resistance alleles and their utility for science moving forward.

Our New Year’s present to the chemical biology community in the form of CRISPR-suppressor scanning with molecular glue degraders. Sounds like a sticky problem, right? But it was no match for Pallavi, Kevin, and the rest of the team!

But wait, there’s more! We have not one, not two, not even three, but four additional stories out on bioRxiv as of today. They’ll be out in journals sometime soon* but if you’re dying to take a look, click on the images below!

*soon: sometime in the next decade, probably (you know how peer review is)

Finally, we are proud to say that all three of our CCB grad students this year passed their PQEs (preliminary qualifying exams) with flying colors! We celebrated with some champagne, though not without some technical difficulties…

Congratulations to Megan, Olivia, and Nicholas!

Anyway, that’s all for today! Keep your eyes peeled for more exciting Liau Lab work just around the corner….!

We'll miss Su!

The winds of change continued to blow this summer as we said goodbye to a true titan of the Liau Lab. A part of the team since day one, Cindy has worn many hats: expert western blotter, pretzel purveyor, novocyte master, birthday cake organizer, ordering guru… it’s safe to say the lab owes Cindy a huge debt of gratitude.

As she embarks on the next phase of her scientific and professional journey, we can’t help but feel a mixture of excited and sad—excited to see a colleague move on to bigger and better things, but sad to be losing another member of the (dysfunctional though still lovable) Liau Lab family.

First Eileen, now Cindy?……So Hoang, farewell…

Best wishes to Cindy, and please visit soon!

Celebrating our very first Ph.D. graduate!

A huge congratulations to Eileen—sorry, Dr. Hoang—for becoming our lab’s very first Ph.D. graduate! One of the first people to join the lab, Eileen is a star chemist and connoisseur of iced coffee. After graduating, she plans to enter the real world as a process chemist at Sanofi.

This is what it looks like to achieve escape velocity from grad school.

Zooming on the big screen! Our newly initiated G1s sit in the front row in rapturous awe, or possibly abject terror upon realizing what the next 5 years have in store.

The group gathers virtually after the defense. Sadly this screenshot missed the boss by just a few seconds!

We’re sad to see Eileen go, but we know she has a bright future ahead of her. We’ll conclude with a quote from Dr. Hoang herself, an oldie but a goodie from the era of the #evening_shift:

Well said, well said.

Happy Holidays from the Liau Lab!

Season’s greetings from your favorite chemical epigenomics lab ;)

This New Year’s Eve, we in the Liau Lab hope that you, your family, and your friends continue to enjoy your holidays and have a great start to the new year! It’s been a year full of challenges and new experiences for all of us, and we owe so much to the healthcare workers, public health officials, and everyone else who has worked to control the pandemic. We are thankful for have had the opportunity to continue our research this past year and beyond :)

Like many others, our lab has been divided into shifts: a morning shift and an evening shift. Luckily for us, we all got to choose the shift that more or less best suits our sleep schedules (or, um, lack thereof). Unsurprisingly, there’s a bit of a difference in the types of people that self-sorted into the two shifts…

Spot-on assessment from Emma. Please note the Comic Sans.

Fig. 1: Representative screenshot illustrating significant morning shift wholesomeness (p < 0.05).

Fig. 2: Representative screenshot illustrating evening shift degeneracy. Results are, of course, not significant.

To help us get accommodate more lab members while still staying at a safe density, our lab was fortunate to annex some new lab space. Take a look!

Thank you to the lab members that graciously accepted banishme— temporary relocation to our annex spaces!

Zoom fatigue? What’s that?

Of course, in an era of distancing and virtual meetings, we’ve been trying to figure out ways to stay connected to each other. Beyond zoom coffee hours, some lab members organized a virtual social over Thanksgiving weekend, where we got to battle for glory in some online games.

Hui Si Kwok, master of deception. Turns out postdoc hands can be used for passaging cells or wiping out your crewmates.

Playing codenames!

Though it was a challenge to adapt our annual holiday party to Zoom, no pandemic was going to get in the way of celebrating another year in Liau Lab history. Thanks to Ceejay for planning this event, and to Emma and others for stepping up to make the annual Year in Review presentation…

it’s fine

Virtual partygoers!

The boss posing with his holiday gift from the lab.

As is traditional, we had a little competition for lab members. This year, Ceejay organized a rousing game of “Brian Bingo”: the game where you predict things Brian will do over Zoom and assemble your own dream bingo board out of them. Although no one got a real bingo, Shelby came the closest. Here’s a look at her winning board:

Red indicates correctly predicted Brian-isms. 5 plus the free space, not bad!

So there you have it! It’s been a long year, and we’ve had our ups and downs, but whether we’re resting or working, we’re trying to do our best to prepare ourselves for the new year.

We’ll leave you with some mouthwatering desserts from Allison’s kitchen:

Allison’s pecan pie.

Allison’s (vegan) pumpkin cheesecake.

Trust us, we’ll need the sugar to get us pumped for the new year. It’s truly been an experience living through 2020, but we’re excited to see what 2021 brings. Until next time, and stay safe!

Virtual Liau Lab

A stillness outside
They gather indoors and think
Thank heavens for zoom

We hope you and your families are all staying healthy and as safe as possible during this uncertain time. Like many others, we in the Liau Lab are doing our part to slow the spread of SARS-CoV-2 by working from home and practicing social distancing. With a pandemic loose, it’s imperative that we all follow the recommendations of our public health officials.

And yet it’s also important to do what we can to stay positive and connected in this time of crisis. In that spirit, we’d like to present this blog post as a glimpse into the little joys of day-to-day quarantine life. Without further ado:

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S T A Y H O M E

an acrostic poem & visual journey

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S — Socializing VIRTUALLY

To stay in touch with others and safeguard our mental health, we’ve been meeting up each week over Zoom to chat and socialize over coffee. Many thanks to Ally for taking the initiative to coordinate these virtual coffee hours!

We may not be essential, but caffeine sure is.

T — TASTY CREATIONS

If there’s one thing that brings our lab together, it’s a love for food, and we have some amazing chefs. Take a look at some of the dishes we’ve made over the past few weeks:

Matzah lasagna made by Allison for Passover. We wouldn’t pass over this dish!

Ramen and scallion pancakes made by Cindy. The dishes are arranged like a water molecule.

Lentils from Pallavi. Have you tried cooking in an Instant Pot?

Potatoes from Pallavi, cooked to goldenrod deliciousness.

A hearty mac and cheese dinner made by Ceejay.

Cinnamon rolls with cream cheese icing made by Nick.

French toast made by Cindy. Look at those swirls!

Pizza made by Cindy. Looks like the toppings have undergone phase separation.

Dalgona coffee made by Hui Si. Beautiful and trendy, just the way we like it in the Liau Lab.

A — ANIMAL FRIENDS

More time at home means more time to spend with our furry pals! Rebecca shared some adorable pictures of her dog, Molly, enjoying her time at home:

Molly posing under a table.

Even dogs can Zoom!

In the midst of the pandemic, we were excited to welcome Emma to the lab as our newest graduate student! Well, excited mostly because now we have access to cute pictures of her adorable cat, Linus. After all, grad students are temporary, but cat pictures are forever.

Welcome to the Liau Lab, Emma and Linus!

Linus posing just for you.

Y — YEARNING FOR THE OUTSIDE WORLD

such good girl am i
now the hooman never leaves
take me on walks tho

Same, Molly, same.

H — Honing the ancient craft of breadmaking

Given the recent nationwide uptick in baking, it’s no surprise that some of our very own lab members have decided to try their hands at making bread. The Liau Lab’s bread and butter, so to speak, are E. coli and human cancer cell lines, so it’s a pretty big deal to see our lab venture into working with yeast.

Ally’s sourdough starter. Does culturing yeast fill the void left by not doing TC?

Sourdough goodness courtesy of Ally. Look at those designs!

More sourdough courtesy of Emma. Notice the pattern in the bread. Like snowflakes or DIY masks, no two loaves are identical.

A fluffy loaf with that classic corgi look, courtesy of Shelby. Shout out to Ally for an emergency contactless delivery of yeast and flour.

O — ONGOING CHOCOLATE ADDICTION

As you all know, our lab really likes chocolate. Just because we’re not in lab, doesn’t mean that addiction went away…

You can tell that Allison baked this banana bread, because it’s clearly just a vehicle for chocolate.

They say to work from home effectively, you need to recreate your office environment. Enter Ally, who decided to recreate the the lab chocolate bowl at home.

M — MEMES

You know we like memes in the Liau Lab. Well, here’s one we concocted at the beginning of the year:

Get you a lab that can do it all.

Meanwhile, some of us are having a little too much fun with the Zoom custom backgrounds…

“This is fine.” Out of the mouths of babes.

E — ENGAGING WITH SCIENCE

They say that cooking is really just science at its heart. Well, Jiaming traded in his round-bottom flasks for some nonstick pots and has been culturing his own yogurt. Testing different brands of milk and carefully varying the freshness of his yogurt starters, he concludes that “they all produce tasty yogurt in different textures and flavors.” Can’t argue with a postdoc.

Homemade yogurt from the Li Test Kitchen. The nice thing about home cooking experiments is that the CCB safety officer will never know if you’re wearing safety glasses or not.

As a lab, we’re also trying to stay engaged with science a little closer to our research. As part of this, we’ve been having weekly journal clubs to cover recent developments and historically important papers in our research areas.

Here’s a view into our virtual lab meetings. Shout out to Shelby and Hui Si for an awesome journal club presentation!

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And that’s all for now. We hope this brought some joy into your day, and thanks for reading! We wish you and your loved ones safety and security.

While we’re sad to be out of the lab for now, we know it’s for the best. We look forward to returning to our benches and hoods in the future so that we can bring more science to you all. Until then (or until our next update), take care!

Spring is blossoming
We wait in a fractured world
For the next blog post

Fall 2018 retrospective

Happy New Year from the Liau Lab! It’s been quiet in the lab the past few weeks, but we’re starting to get into the gear of the new year. In the spirit, however, of holiday season reflection (and since a blog post is severely overdue!) we’ll be taking a look at some of the highlights of fall 2018. Buckle in, cause it’s gonna be a long ride.

First up, the Mid-Autumn Festival! The group celebrated with some tea and mooncakes, courtesy of Cindy.

Not too long after that came another reason to celebrate, when Ally passed her preliminary qualifying exam! Congratulations, Ally!

Speaking of celebrations, we all got more than our fair share of cake with all the birthdays happening in the fall…

For Thanksgiving, Brian graciously welcomed us to his home for a potluck party. As with all potlucks, the quality of the experience is only as good as the quality of cooking your guests can achieve, but luckily for us, we have lots of talented chefs in our lab!

Warning: don’t view the following slideshow on an empty stomach…

…it was a fun night. Of course, in addition to all this eating, we did manage to get some work done. Our lab loves next-generation sequencing, but it’s not every day that we buy a brand new kit. As Kevin found out, they come packaged in huge boxes. Big boxes for big science, right?

As many of you might know, one big focus of our lab is studying the 3D organization of the genome. It’s not something you think about every day, but how the cell fits 2 meters of DNA inside its nucleus is pretty mindblowing. We got the opportunity to share our science with local students, crafting some interactive displays to help illustrate what we do and why we do it. Thank you to the Harvard Ed Portal, and to Brian, Shelby, and Allison for organizing this!

To close out 2018, we enjoyed a holiday party hosted by Brian, where we once again ate plenty of food. Highlights of the evening included a 2018 year-in-review slideshow, as well as a rousing game of white elephant. Here are some highlights from the evening:

And here we are, at the beginning of another year. As we all try to shake off the holiday stupor and get back to work, one thing’s for certain: the new year has much more food in store. After all, we are the Liau Lab.

And with that, thanks for reading! We’re looking forward to some exciting stuff in 2019, and we can’t wait to share it. Until next time :)

Hello there fall!

Charging head first into the new year. It's been a while since our last blog post, but that's not to say the last few weeks haven't been eventful. Besides running experiments, making figures, and submitting grants, we've been up to a lot. Check it out below!

With teaching, classes, rotators, and more awaiting at the start of the academic year, the lab celebrated the waning summer days with a trip out of Cambridge to get dim sum and boba. Despite the challenge of identifying vegetarian-friendly items (not trivial when it comes to Chinese food), we all left with full stomachs. It was even some people's first time trying boba!

As August turned into September, we had another festive occasion: Amanda's birthday! Since she's not a huge fan of cake, Brian bought some pies from a local bakery, Petsi Pies, to help celebrate.

Now that the academic year has begun, we're all steeling ourselves for a busy semester. Recently, posters have been popping up around the chemistry department advertising the fall open houses for different labs. Ours is still quite a while away, but we couldn't resist pinning up some posters in the meantime. We'll leave you with our teaser:

Happy birthday to Cindy (and 4th of July!)